Candidate Genes
Candidate Genes
Genes Implicated in the Etiology of ADHD
The aim of scientific research into any disorder is to identify the causative factors. These factors can be genetic, environmental or a mixture of both. Also the genetic and environmental factors may interract with each other in ways which are confusing to investigation. Unfortunately, ADHD is one such disorder in which the etiology appears to be due to a mixture of environment and genetics. Not only that but it would appear to be polygenic in that inheritance is due a combination of many genes. This makes locating the genetic influences on ADHD all the more difficult as each gene involved may have only a small effect and thus be very dificult to detect. Also there may not be a gene which on its own is enough to always bring about ADHD syptomatology.
Many genetic studies have been performed nonetheless and many candidate genes found in various pathways including the dopamine system, the serotonin system, and the adrenalin system. To date the most commonly replicated associations are with the DAT1 and DRD4 genes in the dopamine system (e.g. Ficks & Waldman, 2009 here). Recently, two new loci have been associated with ADHD, namely monoamine oxidase A (MAO-A) and adrenergic alpha2A receptor gene (ADRA2A). While the first two genes have been very well explored over several years, these latter two have only really been implicated in publications since 2006 and more replicative work needs to be done to confirm the findings made so far. In addition to these genes, another four commonly named in the ADHD literature are 5-HTT, DBH, DRD5, and SNAP-25 (e.g. Coghill & Banaschewski, 2009 here). Good evidence exists for all of these but not to the same extent as for DAT1 and DRD4 in that there has been less clear replication.
Below are details of the above genes arranged as follows:
- Gene: The gene name and chromosomal location
- Allele: The allele linked to ADHD
- Ensembl: A diagram showing the position of the gene on its chromosome on the Ensembl site
- Genecard: A table showing information about the gene from the Weizmann Institute's Genecard database
- Recent Reference: Link to the abstract of the most recently published paper investigating the gene
Gene: DAT1 at 5p15.3
Allele: 480bp long
[Ensembl picture] [Genecard]
Recent Reference:
Genes Brain Behav. 2009 Dec 17 (Abstract)
A Genetic Study of ADHD and Activity Level in Infancy.
Ilott N, Saudino KJ, Wood A, Asherson P.
Gene: DRD4 at 11p15.5
Allele: 7-repeat and 120-bp duplication
[Ensembl picture] [Genecard]
Recent References:
Soc Cogn Affect Neurosci. 2009 Dec 17. (Abstract)
ADHD and the DRD4 exon III 7-repeat polymorphism: an international meta-analysis.
Nikolaidis A, Gray JR.
Am J Med Genet B Neuropsychiatr Genet. 2008 Apr 5;147(3):397-402. (Abstract)
An exploratory study of the relationship between four candidate genes and neurocognitive performance in adult ADHD.
Boonstra AM, Kooij JJ, Buitelaar JK, Oosterlaan J, Sergeant JA, Heister JG, Franke B.
Gene: MAO-A at Xp11.23
Allele: G-allele of 941G/T SNP
[Ensembl picture] [Genecard]
Recent Reference:
Psychiatr Genet. 2009 Dec;19(6):312-9. (Full)
Psychopathy trait scores in adolescents with childhood ADHD: the contribution of genotypes affecting MAOA, 5HTT and COMT activity.
Fowler T, Langley K, Rice F, van den Bree MB, Ross K, Wilkinson LS, Owen MJ, O'Donovan MC, Thapar A.
Gene: ADRA2A at 10q25.2
Allele: G-allele of 1291C/G SNP
[Ensembl picture] [Genecard]
Recent Reference:
Biol Psychiatry. 2009 Apr 1;65(7):564-70 (Abstract)
Association between homozygosity of a G allele of the alpha-2a-adrenergic receptor gene and methylphenidate response in Korean children and adolescents with attention-deficit/hyperactivity disorder.
Cheon KA, Cho DY, Koo MS, Song DH, Namkoong K.
Gene: 5-HTT at 17q11.2
Allele: 5-HTTLPR, and VNTR in intron 2, a SNP in the 3' untranslated region.
[Ensembl picture] [Genecard]
Recent References:
World J Biol Psychiatry. 2009;10(4 Pt 2):581-5. (Abstract)
Development of 5-HT transporter density and long-term effects of methylphenidate in an animal model of ADHD.
Roessner V, Manzke T, Becker A, Rothenberger A, Bock N.
J Neural Transm. 2007 Apr;114(4):513-21 (Abstract)
Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample.
Heiser P, Dempfle A, Friedel S, Konrad K, Hinney A, Kiefl H, Walitza S, Bettecken T, Saar K, Linder M, Warnke A, Herpertz-Dahlmann B, Schafer H, Remschmidt H, Hebebrand J.
Gene: DBH at 9q34.2
Allele: TaqI A2 allele
[Ensembl picture] [Genecard]
Recent References:
Cell Mol Neurobiol. 2009 Sep 16. (Abstract)
Study on DBH Genetic Polymorphisms and Plasma Activity in Attention Deficit Hyperactivity Disorder Patients from Eastern India.
Bhaduri N, Sarkar K, Sinha S, Chattopadhyay A, Mukhopadhyay K.
J Psychiatry Neurosci. 2009 Mar;34(2):88-101. (Abstract)
Candidate genes and neuropsychological phenotypes in children with ADHD: review of association studies.
Kebir O, Tabbane K, Sengupta S, Joober R.
Gene: DRD5 at 4p16.1
Allele: 148 bp
[Ensembl picture] [Genecard]
Recent References:
Psychiatr Genet. 2009 Feb;19(1):57. (Abstract)
Shorter dinucleotide repeat length in the DRD5 gene is associated with attention deficit hyperactivity disorder.
Kim BN, Kang D, Cho SC, Park TW, Lim MH, Chung YC, Kim JW, Hwang JW, Yoo HJ, Chung US, Son JW, Yang JC, Chung SK, Lee JY, Jung YW.
Eur Child Adolesc Psychiatry. 2009 Jan;18(1):26-32. (Abstract)
Molecular genetic contribution to the developmental course of attention-deficit hyperactivity disorder.
Langley K, Fowler TA, Grady DL, Moyzis RK, Holmans PA, van den Bree MB, Owen MJ, O'Donovan MC, Thapar A.
Gene: SNAP-25 at 20p11.2 or 20p12.3
Allele: Dde1 polymorphisms
[Ensembl picture] [Genecard]
Recent References:
Hum Genet. 2009 Jul;126(1):51-90. (Abstract)
Candidate gene studies of ADHD: a meta-analytic review.
Gizer IR, Ficks C, Waldman ID.
Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):781-90. (Abstract)
Investigation of variation in SNAP-25 and ADHD and relationship to co-morbid major depressive disorder.
Kim JW, Biederman J, Arbeitman L, Fagerness J, Doyle AE, Petty C, Perlis RH, Purcell S, Smoller JW, Faraone SV, Sklar P.
